Microsatellite instability and loss of heterozygosity at chromosomes 9 and 17 in non-small cell lung cancer

Abstract

Background: Microsatellite instability (MI) and loss of heterozygosity (LOH) are described in lung cancer specimens. However, their importance in tumorigenesis remains unknown. The aim of this study was to identify the presence of MI and LOH in human tumor and normal bronchial mucosa DNA.

Methods: We performed biopsies with fiberoptic bronchoscopy and took specimens from the tumor and from the opposite site normal bronchial mucosa in 20 patients with non-small-cell lung cancer (NSCLC). Four patients had an adenocarcinoma, while 16 had a squamous cell carcinoma. Also, 6 patients had an early-stage disease (stages I and II), while 14 patients had an advanced-stage disease (stages III and IV). All paired specimens were studied for MI and LOH on chromosome 17p, 17q, 9p, and 9q, with 10 polymorphic markers.

Results: Sixteen of 20 tumors displayed genetic alterations (80%). Six tumors (30%) exhibited MI, five tumors (25%) exhibited LOH, while five tumors exhibited MI and LOH concurrently. The marker HBX had the most frequent incidence of LOH (4/20, 20%), indicating that the hbx gene becomes a strong candidate tumor suppressor gene, whereas of MI it was D17S515 (4/20, 20%). No relationship was observed between the presence of LOH or MI and the histologic subtype of NSCLC or the stage of the disease.

Conclusion: Results suggest that genetic alterations exist in tumor, compared with the normal mucosa DNA. They may have a role in carcinogenesis as they exist in all stages and in both NSCLC histologic subtypes studied.